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Targeted Therapy

Targeted Therapy for Solid Tumors

Phase 2

Recruiting

Led By James M Ford

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have progressed on at least one line of standard systemic therapy OR

Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 8 years

Awards & highlights

No Placebo-Only Group

Summary

This trial helps cancer patients find treatments tailored to their unique genetic makeup. It could improve their outcomes.

Who is the study for?

This trial is for adults with advanced solid tumors that have spread and are not responding to standard treatments or lack treatment options proven to extend life. Participants need available tumor tissue samples, must be in fair health (ECOG 0-2), and willing to undergo genetic testing of their tumors. It's not suitable for those who've had a good response to recent therapies.

What is being tested?

The ComboMATCH trial tests targeted therapies based on genetic mutations in patients' tumors. Various drugs like Oxaliplatin, Ipatasertib, and Olaparib are matched with specific genetic changes identified through testing. The study aims to control the tumor growth by personalizing treatment plans.

What are the potential side effects?

Potential side effects depend on the specific medication given but can include nausea, fatigue, skin reactions, blood count changes, heart issues detected by scans or echocardiography, liver function alterations monitored by MRI/CT scans, and possible discomfort from biopsies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition worsened after at least one standard treatment.

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I am over 18 and can provide a sample of my tumor for research if I join the trial.

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I haven't had significant tumor shrinkage after my last treatment.

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I am under 18 and can provide a sample of my tumor for research if I join the trial.

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My cancer tissue samples are available for testing.

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My condition has no proven treatment to extend life.

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I am 18 or older and can have a low-risk biopsy for research if I join a ComboMATCH trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 8 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 8 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 8 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Accrual of patients to ComboMATCH treatment trials

Assignment of patients to ComboMATCH treatment trials

Enrollment rates to ComboMATCH treatment trials

Secondary study objectives

Therapeutic procedure

Other study objectives

Concordance between whole exome sequencing (WES) and results from the Designated Laboratory (DL)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

20Treatment groups

Experimental Treatment

Active Control

Group I: EAY191-S3 (activating AKT mutation)Experimental Treatment6 Interventions

Patients receive paclitaxel IV and ipatasertib PO on study. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and follow-up.

Group II: EAY191-N5 Arm II (neratinib maleate,palbociclib)Experimental Treatment8 Interventions

Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

Group III: EAY191-N4 Arm I (RAS pathway mutations)Experimental Treatment9 Interventions

Patients receive selumetinib PO and olaparib PO on study. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.

Group IV: EAY191-N2 Cohort II (NF1 mutations)Experimental Treatment9 Interventions

Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.

Group V: EAY191-N2 Cohort I (Arm II) (NF1 mutations)Experimental Treatment8 Interventions

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.

Group VI: EAY191-N2 Cohort I (Arm I) (NF1 mutations)Experimental Treatment9 Interventions

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.

Group VII: EAY191-E5 Cohort II (sotorasib)Experimental Treatment6 Interventions

Patients receive combination therapy as in EAY191-E5 Arm A.

Group VIII: EAY191-E5 Cohort I Arm A (sotorasib, panitumumab)Experimental Treatment6 Interventions

Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

Group IX: EAY191-E4 (taxane therapy)Experimental Treatment6 Interventions

Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.

Group X: EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)Experimental Treatment11 Interventions

Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated

Group XI: EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)Experimental Treatment11 Interventions

Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.

Group XII: EAY191-A3 Monotherapy Cohort 1 (binimetinib)Experimental Treatment6 Interventions

Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

Group XIII: EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)Experimental Treatment6 Interventions

Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

Group XIV: EAY191-A2 (Cohort 3, Arm D)Experimental Treatment7 Interventions

Cohort 3, Arm D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XV: EAY191-A2 (Cohort 2, Arm C)Experimental Treatment7 Interventions

Cohort 2, Arm C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XVI: EAY191-A2 (Cohort 2, Arm B)Experimental Treatment8 Interventions

Cohort 2, Arm B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XVII: EAY191-A2 (Cohort 1, Arm A)Experimental Treatment8 Interventions

Cohort 1, Arm A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XVIII: EAY191-N5 Arm I (neratinib maleate)Active Control7 Interventions

Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

Group XIX: EAY191-E5 Cohort I Arm B (sotorasib)Active Control5 Interventions

Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

Group XX: EAY191-N4 Arm II (RAS pathway mutations)Active Control8 Interventions

Patients receive selumetinib PO on study. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Selumetinib Sulfate

2017

Completed Phase 2

~80